小柯机器人

日本大阪大学Yukinori Okada课题组对676,000名个体进行的跨生物库分析阐明了复杂性状的多基因风险评分（PRS）与人类寿命之间的关联。相关论文于2020年3月23日发表于国际学术期刊《自然-医学》杂志上。

他们与全球三大生物数据库（（ntotal = 675,898；日本生物数据库（n = 179,066），英国生物数据库（n = 361,194）和FinnGen（n = 135,638））合作研究了复杂性状的遗传易感性与人类寿命之间的关系。与观察性研究不同，在观察性研究中很难识别因果关系，PRS可以帮助识别影响人类寿命的驱动生物标志物。具有高收缩压的PRS在跨种族时会遗传较短寿命（危险比= 1.01.03 [1.02-1.04]，Pmeta = 3.9×10-13）和亲代寿命（危险比= 1.06 [1.06-1.07]，P = 2.0××10-86）。肥胖症的PRS对日本和欧洲人的寿命显示出明显的影响（BMI的生发性= 9.5×10-8）。孟德尔随机研究进一步证实了血压和肥胖与寿命的因果关系。除基因型与表型的关联外，他们的跨生物库研究还为PRSs在优化风险因素方面提供了新的价值，这些风险因素可能是提高群体健康的潜在医学治疗目标。

据了解，尽管PRS有望通过先天性健康风险的预测转化为临床实践，但仍需采取一项策略，利用遗传学对驱动健康预后的可改变风险因素进行优化。

附：英文原文

Title: Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan

Author: Saori Sakaue, Masahiro Kanai, Juha Karjalainen, Masato Akiyama, Mitja Kurki, Nana Matoba, Atsushi Takahashi, Makoto Hirata, Michiaki Kubo, Koichi Matsuda, Yoshinori Murakami, Mark J. Daly, Yoichiro Kamatani, Yukinori Okada

Issue&Volume: 2020-03-23

Abstract: While polygenic risk scores (PRSs) are poised to be translated into clinical practice through prediction of inborn health risks1, a strategy to utilize genetics to prioritize modifiable risk factors driving heath outcome is warranted2. To this end, we investigated the association of the genetic susceptibility to complex traits with human lifespan in collaboration with three worldwide biobanks (ntotal=675,898; BioBank Japan (n=179,066), UK Biobank (n=361,194) and FinnGen (n=135,638)). In contrast to observational studies, in which discerning the cause-and-effect can be difficult, PRSs could help to identify the driver biomarkers affecting human lifespan. A high systolic blood pressure PRS was trans-ethnically associated with a shorter lifespan (hazard ratio=1.03[1.02–1.04], Pmeta=3.9×1013) and parental lifespan (hazard ratio=1.06[1.06–1.07], P=2.0×1086). The obesity PRS showed distinct effects on lifespan in Japanese and European individuals (Pheterogeneity=9.5×108 for BMI). The causal effect of blood pressure and obesity on lifespan was further supported by Mendelian randomization studies. Beyond genotype–phenotype associations, our trans-biobank study offers a new value of PRSs in prioritization of risk factors that could be potential targets of medical treatment to improve population health.

DOI: 10.1038/s41591-020-0785-8

Source: https://www.nature.com/articles/s41591-020-0785-8

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex